A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM)

Phase 1

Terminated

Conditions: Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Multiple Myeloma

Interventions: Drug: GS-9219

Registration Number: NCT00499239

Lead Sponsor: Gilead Sciences

Brief Summary: Multi-center, open-label, single-dose, dose-escalating Phase I/II study of GS 9219 in adult patients with relapsed or refractory CLL, NHL or MM. Patients will be enrolled into the study in sequential dose cohorts.

Patients will be administered a single IV infusion of GS 9219 on Day 1 of a 21 day cycle and may receive a total of six treatment cycles based on toxicities and response. Patients who demonstrate disease progression will be discontinued from the study. Patients who, at the completion of six treatment cycles, tolerate treatment and show evidence of disease control (response or stabilization) will be eligible to continue receiving treatment at the same dose.

Detailed Description: The primary objective of this study is as follows:

To assess the safety, toxicity, and maximum tolerated dose (MTD) of GS 9219 administered via IV administration once every three weeks (21 days) for six treatment cycles, i.e. for a total of 18 weeks, in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM).

The secondary objectives of this study are as follows:

To determine the pharmacokinetic parameters of GS 9219 for this regimen and patient population.

To assess the antitumor activity of GS 9219 based on Response Rate and Duration of Response. Progression-free Survival and Overall Survival will be assessed if applicable.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 32

Inclusion Criteria

Relapsed or refractory CLL, NHL or MM
ECOG Performance Status of 0, 1, or 2
Adequate organ function (protocol defined)
ECG without evidence of clinically significant ventricular arrhythmias

Exclusion Criteria

AIDS-related lymphoma
Subjects with NHL who present exclusively with non-measurable lesions
Subjects with MM who have non-secretory and/or non-measurable disease
Recent anticancer therapy (chemotherapy, radiotherapy, and/or biotherapy)within four weeks prior to starting treatment
Evidence of pulmonary fibrosis
Other concurrent malignancy
Uncontrolled concurrent illness
Receiving chronic, systemically administered steroids
Known hypersensitivity to nucleoside analogues

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GS-9219	GS-9219	Escalating doses of GS-9219 (5, 8, 11.5, 16, 22.5, 31.5, 44, and 61.5 mg/m\^2) until determination of the maximum tolerated dose (MTD)

Primary Outcome Measures

Name	Time	Method
Determination of MTD	All visits	Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE). The MTD will be the highest dose level immediately below the dose level where two or more of three to six patients experience a dose-limiting toxicity (DLT).

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of GS-9219 and its metabolites	AAA) CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6	Pharmacokinetics (Cmax, Tmax, Clast, Tlast, λz, t1/2, AUClast, AUCinf, and %AUCexp) measured by blood sampling
Response rate	CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6	Response rate measured by: * CLL: National Cancer Institute Working Group (NCIWG) criteria * NHL - National Cancer Institute (NCI) criteria; Response Evaluation in * MM - International Myeloma Working Group (IMWG) criteria.
Duration of response	CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6	Duration of response measured by: * CLL: National Cancer Institute Working Group (NCIWG) criteria * NHL - National Cancer Institute (NCI) criteria; Response Evaluation in * MM - International Myeloma Working Group (IMWG) criteria.

Trial Locations

Locations (20): Federal State Institution Russian Research Center of Radiology and Surgical Technologies under the Federal Agency for High-Tech Medical Care
🇷🇺
St. Petersburg, Russian Federation
State Public Medical Institution of Novosibirsk Region: State Novosibirsk Regional Clinical Hospital
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Novosibirsk, Russian Federation
Northwestern University
🇺🇸
Chicago, Illinois, United States
State Institution Hematological Research Center under the Russian Academy of Medical Sciences
🇷🇺
Moscow, Russian Federation
UCSF
🇺🇸
San Francisco, California, United States
Nevada Cancer Institute
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Las Vegas, Nevada, United States
State institution Main Military Clinical Hospital n.a.academician N.N. Burdenko under the Ministry of Defense of Russia
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Moscow, Russian Federation
Non-State Medical Institution Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC "Russian Railways"
🇷🇺
Moscow, Russian Federation
State Institution: Medical Radiological Research Center under the Russian Academy of Medical Sciences
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Kaluga Region, Russian Federation
Moscow State Medical Institution: Municipal Clinical Hospital n.a. S.P. Botkin
🇷🇺
Moscow, Russian Federation
Federal State Institution: Research Institute of Hematology and Blood Transfusion under Federal Agency for High-Tech Medical Care
🇷🇺
St Petersburg, Russian Federation
State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development, Institute of Hematology and Transplantology n.a. R.M. Gorbacheva
🇷🇺
St. Petersburg, Russian Federation
State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development
🇷🇺
St. Petersburg, Russian Federation
Fakultni nemocnice Olomouc
🇨🇿
Olomouc, Czech Republic
Fakultni nemocnice Brno - Bohunice
🇨🇿
Brno, Czech Republic
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Fakultni nemocnice Kralovske Vinohrady
🇨🇿
Praha, Czech Republic
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Czech Republic
Vseobecna fakultni nemocnice
🇨🇿
Praha, Czech Republic
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States